This invention relates generally to novel sol-gel derived bioactive glasses containing sodium and uses thereof.
Sol-gel processes for making, bioactive glass using sol-gel technology are generally known. For example, U.S. Pat. No. 5,074,916 (the “'916 patent”), the subject matter of which is incorporated herein by reference, discloses sol-gel processing techniques used to produce alkali-free bioactive glass compositions based on SiO2, CaO2 and P2O5. The '916 patent discloses that by varying the SiO2 content a range of hydroxyapatite production rates can be obtained. Also, varying the time of exposure to actual or simulated in vivo solutions permits use of a range of allowable proportions of SiO2. The sol-gel derived compositions disclosed in the '916 patent can be chosen to achieve target values for a thermal expansion coefficient, elastic modulus and volume electrical resistivity. Methods of manufacturing near equilibrium dried sol-gel bioactive glasses are described in U.S. Pat. No. 6,171,986 herein incorporated by reference in its entirety.
The '916 patent explains that one of the advantages of sol-gel derived bioactive glasses over melt derived, is that the use of alkali metal oxides such as Na2O can be avoided in sol-gel derived bioactive glasses. Such alkali metal oxides serve as a flux or aid in melting or homogenization. The '916 patent points out that the presence of alkali metal oxide ions results in a high pH at the interface between the glass and surrounding fluid or tissue in vivo, and that this can induce inflammation and shut down repair. The '916 patent avoids such issues by using only SiO2, CaO2 and P2O5 and eliminating the traditional need for sodium or other alkali metal compounds to assist in producing bioactivity.
Patent Application Publication U.S. 2009/0208428 states that the presence of the alkali metals, sodium and potassium, at high concentrations in the bioactive glasses can reduce the usefulness of the bioactive glass in vivo. The preferred sol-gel derived glass disclosed in U.S. 2009/0208428 includes strontium and is alkali-metal free.
Bioglass, melt-derived with code name 45S5, contains 45% SiO2 in weight percent with 24.5% CaO, 24.5% Na2O and 6% P2O5, and provides a rapid biological response, or in other words, fast bioactivity, when implanted in living tissue as compared to other bioactive glass formulations.
It has been well recognized that the surface reactivity of Bioglass is attributed to its bioactivity. In the early of 1990s, sol-gel bioactive glasses have been reported with higher specific surface area from their porous structure. Since then, 49S, 58S, 68S, 77S, 86S sol-gel compositions have been reported with corresponding 50%, 60%, 70%, 80% and 90% SiO2 in mole percent, respectively. The specific surface area of all of these compositions is more than 100 times greater than melt-derived 45S5 Bioglass. These compositions typically do not contain Na2O due to the difficulty in incorporating the Na2O into the glass network.
Some hemostasis products used worldwide, such as Zeolite and starch powders derived products, owe their hemostatic effect to high specific surface area. It is believed that materials with high surface area adsorb water from the blood rapidly and concentrate clotting proteins and platelets to promote instantaneous clot formation. Sol-gel bioactive glasses possess much higher specific surface area, and should be ideal hemostasis materials in addition to their recognized properties of enhancing bone growth, soft tissue growth and healing as well as oral care in applications such as tooth desensitization, anti-gingivitis and tooth whiting. U.S. Patent Application Publication Nos. 2009/0186013 and 2009/0232902, herein incorporated by reference in their entirety, claim that sol-gel made bioactive silica gel with porous structure and high specific surface area, possessed hemostatic effect. But all of the silica gels reported were made from Si, Ca and P precursors or their inorganic compounds and none of silica gels were reported with a sodium precursor.
A few articles have been published recently on sol-gel derived 45S5 Bioglass containing Na2O. See Q Z Chen, Y Lia, L Y Jina, J M W Quinnc, P A Komesaroffe, “A new sol-gel process for producing Na2O-containing bioactive glass ceramics”, Acta Biomaterialia V6(10), 4143-53, 2010; R L Siqueira, O P Edgar and D Zanotto, “Gel-derived SiO2-CaO—Na2O—P2O5 bioactive powders: Synthesis and in vitro bioactivity”, Materials Science and Engineering: C V 31(5), 983-91, 2011; Q Z Chen, G A Thouas, “Fabrication and Characterization of Sol-gel Derived 45S5 Bioglass—Ceramic Scaffolds”, Acta Biomaterialia, 7, 3636-26, 2011; I Cacciotti, M Lombardi, A Bianco et al., “Sol-gel Derived 45S5 Bioglass: Synthesis, Microstructural Evolution and Thermal Behaviour”, J Mater Sci: Mater Med, 23:1849-66, 2012. All of those works used NaNO3 (sodium nitrate) to introduce Na2O into the Bioglass system during the sol-gel processing. As explained below, a comparative experiment demonstrated that the precipitation could be seen visually on the gel's surface prepared with sodium nitrate after aging, which could result in possible non-homogenous composition. The exact compositions of the reported sol-gel 45S5 Bioglass materials remain a question since no data has been reported in those published works. Also, all of those articles describe the use of high temperature sintering from 700° C. to 1100° C. to prepare the sol-gel 45S5 glass. The high temperature sintering could enable the preparation of a homogenous composition, however this process could reduce the surface area dramatically to yield a dense 45S5 Bioglass. The authors do not provide any porosity and surface area data in these publications.